Primate population dynamics in Ngogo, Kibale National Park, Uganda, over nearly five decades.
Many anthropogenic-driven changes, such as hunting, have clear and immediate negative impacts on wild primate populations, but others, like climate change, may take generations to become evident. Thus, informed conservation plans will require decades of population monitoring. Here, we expand the duration of monitoring of the diurnal primates at Ngogo in Kibale National Park, Uganda, from 32.9 to 47 years. Over the 3531 censuses that covered 15,340 km, we encountered 2767 primate groups. Correlation analyses using blocks of 25 census walks indicate that encounters with groups of black and white colobus, blue monkeys, and baboons neither increased nor decreased significantly over time, while encounters with groups of redtail monkeys and chimpanzees marginally increased. Encounters with mangabeys and L'Hoesti monkeys increased significantly, while red colobus encounters dramatically decreased. Detailed studies of specific groups at Ngogo document changes in abundances that were not always well represented in the censuses because these groups expanded into areas away from the transect, such as nearby regenerating forest. For example, the chimpanzee population increased steadily over the last 2 + decades but this increase is not revealed by our census data because the chimpanzees expanded, mainly to the west of the transect. This highlights that extrapolating population trends to large areas based on censuses at single locations should be done with extreme caution, as forests change over time and space, and primates adapt to these changes in several ways.


Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system.
Hepatocellular carcinoma (HCC), the fifth most common cancer that predominantly occurs in liver cirrhosis patients, requires staging systems to design treatments. The barcelona clinic liver cancer staging system (BCLC) is the most commonly used HCC management guideline. For BCLC stage B (intermediate HCC), transarterial chemoembolization (TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0 (very early HCC), TACE could be an alternative for patients unsuitable for radiofrequency ablation (RFA) or hepatic resection. In patients with BCLC stage A, TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B, TACE provides survival benefits compared with supportive care options. However, because of the substantial heterogeneity in the patient population with this stage, a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally, TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together, TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.


[Clinical study of the pars plana Ahmed glaucoma valve implant in refractory glaucoma patients].
To evaluate the effect of pars plana implantation of the Ahmed glaucoma valve on refractory glaucoma. Five patients (5 eyes) (3 men, 2 women) were fitted with the Ahmed glaucoma valve. Mean age was 51.8 21.3 years, and mean follow-up was 9.4 +/- 2.6 months. Among the 5 eyes studied, 4 eyes were in neovascular glaucoma patients. Of these 4 eyes, 2 eyes were in diabetic retinopathy patients and 2 eyes were in a patient with central retinal vein occlusion. The remaining eye was in a developmental glaucoma patient. As a surgical procedure after pars plana vitrectomy, the inlet tube of the Ahmed glaucoma valve was placed in the posterior chamber. The mean preoperative IOP of 46.8 +/- 15.7 mmHg (30-64 mmHg) under maximum tolerable medication was reduced to 16.0 +/- 2.0 mmHg (14-19 mmHg) after surgery. Postoperative visual acuity improved in 3 eyes, and the mean visual acuity in these eyes improved from 0.05 +/- 0.09 (sl.-0.07) to 0.17 +/- 0.3(0-0.7). A reduction in visual acuity was observed in 2 eyes; in one, due to retinal detachment, and in the other, due to transient high IOP and vitreous hemorrhage. The visual acuity improved in 60% of patients and the IOP controlled in 80% of patients. The implantation of the Ahmed glaucoma valve for refractory glaucoma was effective in our study.


A facile synthesis of deaza-analogues of the bisindole marine alkaloid topsentin.
A series of substituted ethyl 1-[(tert-butoxycarbonyl)amino]-2-methyl-5- (1-methyl-1H-indol-3-yl)-4-[(1-methyl-1H-indol-3-yl)carbonyl]-1H-pyrrole-3-carboxylates were prepared in excellent yields (82-98%) by one-pot reactions between β-dicarbonyl compounds 12a-e and 1,2-diaza-1,3-diene (DD) 13. Derivatives 10a,c-e, deazaanalogues of the bis-indole alkaloid topsentin, screened by the National Cancer Institute (Bethesda, MD, USA) in the in vitro one dose primary anticancer assay against a panel of about 60 human tumor cell lines, showed no significant activity, with the exception of compound 9e, which showed moderate activity against the HOP-92 cell line of the non small cell lung cancer sub-panel and the SNB-75 cell line of the CNS sub-panel.


Basic and interleukin-2-augmented natural killer cell activity in lichen planus.
Natural killer cell (NK) activity of peripheral blood lymphocytes against K 562 cells was investigated in lichen planus (LP). 38 LP patients with cutaneous or oral mucosal involvement and 20 healthy controls participated in the study. A statistically significant decrease in the NK response in LP patients with extensive erosive oral mucosal involvement (p less than 0.02) and in generalized acute eruptive LP (p less than 0.01) was noted compared to those with nonerosive LP of the oral mucosa or healthy controls. Interleukin 2 failed to restore completely the reduced NK activities in our patients with LP.


Effects of Composites Containing Bioactive Glasses on Demineralized Dentin.
The aim of this study was to evaluate the degradation of completely demineralized dentin specimens in contact with a filler-free or 2 ion-releasing resins containing micrometer-sized particles of Bioglass 45S5 (BAG) or fluoride-containing phosphate-rich bioactive glass (BAG-F). Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were also used to evaluate the remineralization induced by the experimental ion-releasing resin-based materials. Dentin beams were totally demineralized in H3PO4 (10%) and placed in direct contact with a filler-free (RESIN) or 2 experimental ion-releasing resins (BAG or BAG-F) and immersed in artificial saliva (AS) up to 30 d. Further specimens were also processed and submitted to FTIR and SEM analysis to evaluate the remineralization induced by such ion-releasing resins before and after AS immersion. BAG and BAG-F alkalinized the incubation media. A significant decrease of the dry mass was observed between the specimens of all groups stored for 3 and 30 d in AS. However, the fluoride-containing phosphate-rich bioactive glass incorporated into a resin-based material (BAG-F) showed greater ability in reducing the solubilization of C-terminal cross-linked telopeptide (ICTP) and C-terminal telopeptide (CTX) after prolonged AS storage. Moreover, after 30 d of AS storage, BAG-F showed the greatest remineralizing effect on the stiffness of the completely demineralized dentin matrices. In conclusion, fluoride-containing phosphate-rich bioactive glass incorporated as micrometer-sized filler in dental composites may offer greater beneficial effects than Bioglass 45S5 in reducing the enzyme-mediated degradation and remineralization of demineralized dentin.


Markovian embedding of non-Markovian superdiffusion.
We consider different Markovian embedding schemes of non-Markovian stochastic processes that are described by generalized Langevin equations and obey thermal detailed balance under equilibrium conditions. At thermal equilibrium, superdiffusive behavior can emerge if the total integral of the memory kernel vanishes. Such a situation of vanishing static friction is caused by a super-Ohmic thermal bath. One of the simplest models of ballistic superdiffusion is determined by a biexponential memory kernel that was proposed by [Bao J. Stat. Phys. 114, 503 (2004)]. We show that this non-Markovian model has infinitely many different four-dimensional Markovian embeddings. Implementing numerically the simplest one, we demonstrate that (i) the presence of a periodic potential with arbitrarily low barriers changes the asymptotic large-time behavior from free ballistic superdiffusion into normal diffusion; (ii) an additional biasing force renders the asymptotic dynamics superdiffusive again. The development of transients that display a qualitatively different behavior compared to the true large-time asymptotics presents a general feature of this non-Markovian dynamics. These transients though may be extremely long. As a consequence, they can be even mistaken as the true asymptotics. We find that such intermediate asymptotics exhibit a giant enhancement of superdiffusion in tilted washboard potentials and it is accompanied by a giant transient superballistic current growing proportional to t(alpha(eff)) with an exponent alpha(eff) that can exceed the ballistic value of 2.


Association of social and clinical conditions to the quality of life of patients with heart failure.
To analyze the association between sociodemographic and clinical conditions with the quality of life related to health of heart failure patients. Cross-sectional study with a non-random sample of 84 outpatients with heart failure, performed in the city of João Pessoa, PB, Brazil, in the period from January to July 2015. The questionnaire by name Minnesota Living with Heart Questionnaire was used The following tests were applied in data analysis: t-Student, ANOVA and Pearson's Correlation, com a 5% significance level. The average scores of the Minnesota Living with Heart Failure Questionnaire showed a good quality of life in the group under study. There was a significant negative association between quality of life and age: thus the lower the age, the worse the quality of life. Health promotion actions become necessary to improve the coping capacity of this disease, especially for younger patients.


The NASA Twins Study: The Effect of One Year in Space on Long-Chain Fatty Acid Desaturases and Elongases.
At present, there is no clear understanding of the effect of long-duration spaceflight on the major enzymes that govern the metabolism of omega-6 and omega-3 fatty acids. To address this gap in knowledge, we used data from the NASA Twins Study, which includes a multiscale omics investigation of the changes that occurred during a year-long (340 days) human spaceflight. Embedded within the NASA Twins data are specific analytes associated with fatty acid metabolism. To examine the long-chain fatty acid desaturases and elongases in a single human during 1 year in space. One male twin was on board the International Space Station (ISS) for 1 year, while his monozygotic twin served as a genetically matched ground control. Longitudinal assessments included the genome, epige-nome, transcriptome, proteome, metabolome, microbiome, and immunome during the mission, as well as 6 months before and after. The gene-specific fatty acid desaturase and elongase transcriptome data (FADS1, FADS2, ELOVL2, and ELOVL5) were extracted from untargeted RNA-seq measurements derived from white blood cell fractions. Most data from the elongases and desaturases exhibited relatively similar expression profiles (R2 >0.6) over time for the CD8, CD19, and lymphocyte-depleted (LD) cell fractions, indicating overall conservation of function within and between the subjects. Both cell-type and temporal specificity was observed in some cases, and some differences were also apparent between the polyadenylated (polyA) fraction of processed RNAs versus the ribodepleted (ribo-) fraction. The flight subject showed a stronger enrichment of the fatty acid metabolic process pathway across almost all cell types (columns, CD4, CD8, CPT, and LD), most especially in the ribodepleted fraction of RNA, but also with the polyA+ fraction of RNA. Gene set enrichment analysis (GSEA) measures across three related fatty acid metabolism pathways showed a differential between the ground and the flight subject. There appears to be no persistent alteration of desaturase and elongase gene expression associated with 1 year in space. However, these data provide evidence that cellular lipid metabolism can be responsive and dynamic to spaceflight, even though it appears cell-type and context specific, most notably in terms of the fraction of RNA measured and the collection protocols. These results also provide new evidence of mid-flight spikes in expression of selected genes, which may indicate transient responses to specific insults during spaceflight.


High-quality genome assembly and genetic mapping reveal a gene regulating flesh color in watermelon (Citrullus lanatus).
The unique color and type characteristics of watermelon fruits are regulated by many molecular mechanisms. However, it still needs to be combined with more abundant genetic data to fine-tune the positioning. We assembled genomes of two Korean inbred watermelon lines (cv. 242-1 and 159-1) with unique color and fruit-type characteristics and identified 23,921 and 24,451 protein-coding genes in the two genomes, respectively. To obtain more precise results for further study, we resequenced one individual of each parental line and an F2 population composed of 87 individuals. This identified 1,539 single-nucleotide polymorphisms (SNPs) and 80 InDel markers that provided a high-density genetic linkage map with a total length of 3,036.9 cM. Quantitative trait locus mapping identified 15 QTLs for watermelon fruit quality-related traits, including β-carotene and lycopene content in fruit flesh, fruit shape index, skin thickness, flesh color, and rind color. By investigating the mapping intervals, we identified 33 candidate genes containing variants in the coding sequence. Among them, Cla97C01G008760 was annotated as a phytoene synthase with a single-nucleotide variant (A → G) in the first exon at 9,539,129 bp of chromosome 1 that resulted in the conversion of a lysine to glutamic acid, indicating that this gene might regulate flesh color changes at the protein level. These findings not only prove the importance of a phytoene synthase gene in pigmentation but also explain an important reason for the color change of watermelon flesh.


[Harvesting of mononuclear cells from peripheral blood in malignant hemopathies].
After demonstrating through animal models that progenitor cells with haemopoietic regenerative capability are present in peripheral blood, such precursor cells were also found in the mononucleated cell (MNC) fraction of human peripheral blood. It was shown that such cells increase in the recuperative period following chemotherapy. A number of studies have demonstrated that autologous infusion of such MNC achieved by cytapheresis may lead to a quick restoration of haemopoiesis. The initial results of peripheral blood MNC achievement in 18 patients with different malignancies of the blood are presented in this paper. Ninety-one cytapheresis sessions were carried out, 88 with a Fenwall CS-3000 continuous-flow machine, and the remaining three with a Haemonetics V-50 discontinuous-flow cell separator. The number of sessions per patient ranged from three to six and the harvested MNC count was 19.3 x 10(9)/L, the percentage of recovery being 56.4%. Some studies are currently in course aimed to analyse the MNC subpopulations in order to measure the progenitor-cell fraction and to establish the viability of such cells for further transplants. Since only five patients have recently been transplanted, all successfully, no definite conclusions can be drawn presently in this connection.


Clinicopathological and immunohistochemical analysis of oral melanocytic nevi and review of the literature.
Oral melanocytic nevi (OMNs) are uncommon benign melanocytic tumors, histologically similar to their cutaneous counterparts. The aim of this study was twofold: to contribute to the epidemiology with a literature review with the first Spanish series of OMNs, and to report on clinicopathological, immunohistochemical and demographic findings. A retrospective analysis of cases attended over the period 1999-2010 was carried out using data drawn from the pathology unit files at two public hospitals in the Spanish region of Andalusia, serving between them a population of 823.614 inhabitants (11%). Ten cases of OMNs were retrieved, accounting for 0.18% of the total 5499 oral biopsies performed over the period. The female-to-male ratio was 1.5:1; mean patient age was 30. The palate was the most common location (70%). Relative frequencies of histologic types were as follows: subepithelial (40%), common blue (30%), compound (20%) and junctional (10%). Immunohistochemical examination showed strong S-100 protein expression, variable reactivity to HMB-45 and high c-Kit expression by junctional melanocytes. Ki-67 was ≤3 in all cases. Although this first clinicopathologic analysis of OMNs reported in Spain was based on a small patient series, the results are in line with those reported in larger series and additionally provide new demographic data. Since OMNs and early melanomas are usually detected at routine dental examination, detailed oral exploration should always be performed, and in case of doubt a biopsy should be taken to ensure an accurate diagnosis.


Compressive Sensing of Roller Bearing Faults via Harmonic Detection from Under-Sampled Vibration Signals.
The Shannon sampling principle requires substantial amounts of data to ensure the accuracy of on-line monitoring of roller bearing fault signals. Challenges are often encountered as a result of the cumbersome data monitoring, thus a novel method focused on compressed vibration signals for detecting roller bearing faults is developed in this study. Considering that harmonics often represent the fault characteristic frequencies in vibration signals, a compressive sensing frame of characteristic harmonics is proposed to detect bearing faults. A compressed vibration signal is first acquired from a sensing matrix with information preserved through a well-designed sampling strategy. A reconstruction process of the under-sampled vibration signal is then pursued as attempts are conducted to detect the characteristic harmonics from sparse measurements through a compressive matching pursuit strategy. In the proposed method bearing fault features depend on the existence of characteristic harmonics, as typically detected directly from compressed data far before reconstruction completion. The process of sampling and detection may then be performed simultaneously without complete recovery of the under-sampled signals. The effectiveness of the proposed method is validated by simulations and experiments.


Silencing of Odorant-Binding Protein Gene OBP3 Using RNA Interference Reduced Virus Transmission of Tomato Chlorosis Virus.
Tomato chlorosis virus (ToCV) is widespread, seriously impacting tomato production throughout the world. ToCV is semi-persistently transmitted by Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Currently, insect olfaction is being studied to develop novel pest control technologies to effectively control B. tabaci and whitefly-borne virus diseases. Despite current research efforts, no report has been published on the role of odorant-binding proteins (OBPs) in insect preference under the influence of plant virus. Our previous research showed that viruliferous B. tabaci preferred healthy plants at 48 h after virus acquisition. In this study, we determined the effect of OBPs on the host preference interactions of ToCV and whiteflies. Our results show that with the increase in acquisition time, the OBP gene expressions changed differently, and the OBP3 gene expression showed a trend of first rising and then falling, and reached the maximum at 48 h. These results indicate that OBP3 may participate in the host preference of viruliferous whiteflies to healthy plants. When the expression of the OBP3 gene was knocked down by an RNA interference (RNAi) technique, viruliferous Mediterranean (MED) showed no preference and the ToCV transmission rate was reduced by 83.3%. We conclude that OBP3 is involved in the detection of plant volatiles by viruliferous MED. Our results provide a theoretical basis and technical support for clarifying the transmission mechanism of ToCV by B. tabaci and could provide new avenues for controlling this plant virus and its vectors.


Field dependence of the electron spin relaxation in quantum dots.
The interaction of the electron spin with local elastic twists due to transverse phonons is studied. The universal dependence of the spin-relaxation rate on the strength and direction of the magnetic field is obtained in terms of the electron gyromagnetic tensor and macroscopic elastic constants of the solid. The theory contains no unknown parameters and it can be easily tested in experiment. At high magnetic field it provides a parameter-free lower bound on the electron spin relaxation in quantum dots.


Adsorption configuration change of pyridine on Ge(100): dependence on exposure amount.
The variations of adsorption configurations of pyridine on Ge(100) as a function of exposure amount have been studied using high-resolution photoelectron spectroscopy (HRPES). At low exposure the C 1s and N 1s core levels show a single adsorption state of pyridine with N 1s binding energy at 400.85 eV and C 1s binding energies at 286.7 and 285.9 eV, respectively. Those are attributable to Ge-N dative bonding of pyridine through the lone pair electrons of its N atom, which is consistent with previous STM and theoretical studies. As the molecular exposure increases the N 1s core level reveals not only the dative-bonding state of pyridine but also the appearance of a new chemical state at 398.80 eV, corresponding to the sigma bonding of Ge-N. Such a change of adsorption configuration agrees well with new C 1s features at the low binding energy side, which accounts for the evolution of cycloaddition products with Ge-C bonds. Consequently, di-sigma-bonded cycloadducts coexist with Ge-N dative-bonding products for the final configuration with high density of pyridine on the Ge(100).


Factors influencing the nighttime activity of old persons in their community.
Individual characteristics and environmental constraints were assessed as influences of the variable frequency of old people's nighttime activity. Data were obtained from structured interviews given to a random sample of 400 persons aged 60 and older living in a middle-class community. Multiple regression analyses revealed that old people who went out more frequently at night had stronger urban and stimulus-seeking environment dispositions, felt more in control of their lives (perceived internal locus of control), were better educated, and were more likely to be employed. They also were less likely to fear going out at night because of crime and had available to them more flexible (automobile) transportation. It is concluded that variability in individual competence or vulnerability alone is not a sufficient basis to explain the variable frequency of old people's nighttime activity.


Hematological parameters immediately after birth in twins and higher order multiples.
To develop reference values for hematological parameters in twins and higher order multiple births immediately after birth and compare them with values from singletons. In this retrospective matched cohort study, hematological parameters immediately after birth from multiples, and gestation- and sex-matched singletons born between 2007 and 2009 were obtained. Infants born with maternal or fetal conditions known to affect hematological values were excluded. Data were compared using Student t-test, chi-square test, and nonparametric tests as appropriate. Three hundred sixty-three multiples were matched with 363 singletons. Multiples had lower birth weights and higher rate of conception by in-vitro fertilization than singletons. Mean (SD) hemoglobin (171 ± 24 vs. 167 ± 23 g/L; p = 0.04) was marginally higher but nucleated red cells were 30% lower (1.7 ± 2.6 vs. 2.6 ± 3.9 10(9)/L, p < 0.01) in multiples. Total white blood cells (WBCs) were 14% lower, absolute neutrophils 30% lower, monocytes 31% lower, basophils 28% lower, and immature WBC 56% lower in multiples. Mean hemoglobin was higher, whereas total WBC, absolute neutrophils, monocytes, and eosinophils were significantly lower in multiples compared with singletons. These differences in WBC and neutrophil counts should be considered when interpreting hematological parameters in multiples.


[Anxiety, depression and dementia].
Approaching the demented patient needs to take into account the affective disorders, as anxiety and depression, which will appear with the dementia. The clinical symptomatology of anxiety and depression in dementia may be unusual or misleading because of the cognitive impairment: anxiety finds more expression with motor agitation than with speech, depression may be masked by behavioral disorders or somatoform symptoms. Anxiety, depression and cognitive defect are overlapped, for example the outcome of the depressive pseudo-dementia may not be as favorable regarding the cognitive dimension as usually assumed. Anxiety and depression in dementia may result from decreased function of the neurotransmission systems in the brain. Psychodynamic interpretation suggests that the dimension impairment involves narcissic defects and archaic beings. Treatment must be global, including biological therapies--as pharmacologic agents (minor tranquilizers, neuroleptics, antidepressants) and ECT--and psychological therapies, focused on affective relationships. The familial support will not be omitted.


Gut Virome: Role and Distribution in Health and Gastrointestinal Diseases.
The study of the intestinal microbiome is an evolving field of research that includes comprehensive analysis of the vast array of microbes - bacterial, archaeal, fungal, and viral. Various gastrointestinal (GI) diseases, such as Crohn's disease and ulcerative colitis, have been associated with instability of the gut microbiota. Many studies have focused on importance of bacterial communities with relation to health and disease in humans. The role of viruses, specifically bacteriophages, have recently begin to emerge and have profound impact on the host. Here, we comprehensively review the importance of viruses in GI diseases and summarize their influence in the complex intestinal environment, including their biochemical and genetic activities. We also discuss the distribution of the gut virome as it relates with treatment and immunological advantages. In conclusion, we suggest the need for further studies on this critical component of the intestinal microbiome to decipher the role of the gut virome in human health and disease.


Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer.
Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC. We demonstrate that the tumor-specific FAP+ fibroblasts and SPP1+ macrophages were positively correlated in 14 independent CRC cohorts containing 2550 samples and validate their close localization by immuno-fluorescent staining and spatial transcriptomics. This interaction might be regulated by chemerin, TGF-β, and interleukin-1, which would stimulate the formation of immune-excluded desmoplasic structure and limit the T cell infiltration. Furthermore, we find patients with high FAP or SPP1 expression achieved less therapeutic benefit from an anti-PD-L1 therapy cohort. Our results provide a potential therapeutic strategy by disrupting FAP+ fibroblasts and SPP1+ macrophages interaction to improve immunotherapy.


Long-term follow-up and final height in girls with central precocious puberty treated with luteinizing hormone-releasing hormone analogue nasal spray.
To evaluate clinical, hormonal, and auxologic features in a group of girls with central precocious puberty during and after long-term treatment with luteinizing hormone-releasing hormone analogue nasal spray. Clinical survey, before-after trial. Pediatric Clinic, Endocrinological Center, University of Bologna (Italy). Forty-one girls with central precocious puberty were treated for 28 months (range, 12 to 60 months); 25 of them discontinued therapy at a mean chronological age of 10.0 +/- 0.9 years and were followed up for 25 months (range, 6 to 50 months). Twelve patients achieved adult height. Buserelin acetate (D-Ser [TBU] LHRH A1-9EA) nasal spray; 1800 micrograms/d subdivided into six intranasal administrations of 300 micrograms each. Basal follicle-stimulating hormone, peak gonadotropin values (fluoro-immunoenzymatic method, Eurogenetics, Tessenderlo, Belgium; sensitivity was 0.5 IU/L for luteinizing hormone and 1 IU/L for follicle-stimulating hormone), and estradiol (radioimmunoassay method, DPC Kit, Los Angeles, Calif; sensitivity was 11.01 pmol/L) were significantly suppressed (P < .0001) as of the third month of treatment and increased significantly (P < .01) to pretreatment levels 6 months after discontinuation of therapy. Uterine and mean ovarian volumes, which were stable throughout treatment, appeared significantly higher (P < .05) than before treatment at only 6 months after stopping therapy. In patients with more advanced bone age (according to Greulich and Pyle) at onset of treatment, we observed a more significant improvement of SD score for height (Tanner). Mean adult height in our patients was 159.5 +/- 6.1 cm, and the variables that were significantly associated with final height were height age/bone age ratio at onset and target height (according to Tanner). Long-term buserelin treatment administered nasally is effective because of completeness of inhibition, quick reversibility after treatment is stopped, and lack of side effects. Its auxologic results are different depending on bone age advancement at onset, which represents a predictor of "therapeutic success." Further follow-up would be useful.


Serious infections in adults following splenectomy for trauma.
Postsplenectomy sepsis in children is a well-recognized hazard. Few reports discuss the risk of sepsis in the asplenic adult. Case reports of 47 adults with serious infections following splenectomy for trauma were examined. We conclude that fulminant sepsis after splenectomy for trauma in adults is indeed a potential risk and that all such patients should receive penicillin prophylaxis and pneumococcal vaccine.


Reduced mortality and moderate alcohol consumption: the phospholipase D-mTOR connection.
Many studies have suggested that moderate alcohol consumption reduces mortality. There is also substantial evidence that lifespan is extended with suppression of TOR (target of rapamycin). It was reported recently that rapamycin is able to extend the lifespan of a mammal--implicating the mammalian TOR (mTOR). mTOR has a requirement for the lipid second messenger phosphatidic acid (PA), which is generated by phospholipase D (PLD). Therefore, in principle, suppression of PLD would be similar to treatment with rapamycin. Significantly, PLD utilizes ethanol preferentially over water in the hydrolysis reaction that ordinarily generates PA. In the presence of ethanol, phosphatidyl-ethanol is generated at the expense of PA leading to the suppression of mTOR. This reaction, known as the transphosphatidylation reaction, provides a mechanistic basis for the reduced mortality observed with moderate consumption of alcohol--that being the suppression of mTOR.


Practice readiness of new graduate nurses and factors influencing practice readiness: A scoping review of reviews.
For many years there has been concern that new graduate nurses may not have been adequately prepared for the workplace, often framed in terms of whether they are work ready or practice ready and able to deal with the 'reality shock' of transitioning from student to clinician. This has prompted significant research to investigate the practice readiness of new graduate nurses. Identify what is known about the practice readiness of new graduate nurses upon commencement of employment, how practice readiness changes over their first year of employment and explore the factors which influence practice readiness. Scoping review of existing reviews guided by the framework developed by Arksey and O'Malley, with search results based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. MEDLINE, CINAHL, PsycINFO, Scopus and Web of Science were searched to identify literature reviews synthesising evidence about new graduate nurses, work readiness, practice readiness, competency and transition to practice. New graduate nurses were defined as nurses who were working in any clinical setting as a nurse within their first year of employment after graduation. Database searching was supplemented with snowball searching and limited to English language papers published between 2011 and 2020. Full-text copies of included reviews were imported into an NVivo (Version 12) database to facilitate analysis and synthesis of findings. Forty-five reviews were included. The findings indicate that transition is influenced by a wide range of intrapersonal, interpersonal and organisational factors, many of which are beyond the control of new graduate nurses. The findings also suggest that, overall, there are no major concerns about the practice readiness of new graduate nurses consistently supported by strong evidence. However, there is evidence to suggest that they 'lack confidence' during the first few months of employment. The 'receptivity' of the clinical environment to new graduate nurses appears to be a critical influence on their experience of transitioning from student to clinician and can also influence their readiness for the role of a registered nurse. Rather than focusing on the question of whether new graduate nurses are adequately prepared for the workplace, it may be time to shift the question to whether the workplace is ready to support new graduate nurses. The findings suggest two research priorities for advancing our understanding of workplace support for new graduate nurses.


Confidentiality and American semen donors.
Most American donor insemination programs include a policy of complete confidentiality concerning the donor of the semen. This is the result of a long legal tradition of American constitutional law. However, some slight abridgement of this body of legal decisions might be very much in the best interests of children arising from donor insemination, and even--in most cases, in fact--the donors themselves. With regard to the children, the factors involved are both those of genetic counseling, should the need arise, and psychological development. Of course, as at present, the donor must be relieved of all responsibility, both legal and financial.


Mercury methylation from mercury selenide particles in soils.
Selenium-inhibited monomethylmercury (MeHg) production is an attractive strategy for mitigating the risks of MeHg exposure. However, it is poorly understood the methylation potential of mercury selenide (HgSe) particles during their aging in soils and sediments. Net MeHg production in three floodplain soils amended with different geochemical species of mercury selenides, i.e., dissolved inorganic mercury freshly mixed with selenite (Hg(II)+Se(IV)), HgSe nanoparticles (45.2 ± 0.5 nm) and microparticles (> 1 μm) is examined. Among mercury types, the methylation from nanoparticulate HgSe was similar to (0.05 - 0.5 % vs. 0.1 - 0.4 %, yellow brown soil) or 12.9 - 21.0 times lower (0.02 - 0.1 vs. 0.6 - 1.5 %, black soil) than that from Hg(II)+Se(IV); however, net MeHg production from HgSe nanoparticles (0.02 - 0.5 %) was 1.9 - 15.5 times greater than HgSe microparticles (< 0.05 %) in all soils. Furthermore, net MeHg production from nanoparticulate HgSe varied significantly among soil types, attributable to differences in soil organic matter contents (2.4-5.8%) and microbial methylator community among soils. These results address the importance of geochemical intermediates of mercury selenide precipitation reactions and soil properties in MeHg production, and develop Se-based remediation strategy to minimize negative effects of MeHg on environmental and human health.


Autoimmune diabetes in 26 villages outside Madras.
Autoimmune diabetes is one of the most common chronic diseases in the world. Autoantibodies against major antigens GAD65 and IA-2 as well as some minor antibodies are markers for autoimmune diabetes already several years before clinical onset in most populations. Screening the population for these autoantibodies can help identify subjects at risk for developing type 1 diabetes. In our study we screened 20,903 inhabitants in 26 villages outside Madras for diabetes. Among them 3.64% were detected to be diabetic. The aim of our study was to detect the presence of glutamic acid decarboxylase (GAD65), tyrosine phosphates (IA-2) and tissue transglutaminase (TTG) antibodies. We studied 169 individuals from this population, 75 of them were diagnosed as diabetics, based on presence of sugar in the urine and an elevated blood sugar, 58 had hypertension, and 36 were healthy subjects. We used radioimmunoassay with in vitro translated and transcribed human recombinant 35S-GAD65, IA-2 and TTG antigens. We observed presence of GAD65Ab in 10%, IA-2Ab in 5%, and TTGAb in 5% in diabetic subjects, while the healthy subjects and people with hypertension didn't carry any of these antibodies. We conclude that prevalence of autoimmune diabetes mellitus based on antibody screening in this population is significantly high.


Production of poly (3-hydroxybutyrate) and extracellular polymeric substances from glycerol by the acidophile Acidiphilium cryptum.
Acidiphilium cryptum is an acidophilic, heterotrophic, and metallotolerant bacteria able to use dissolved oxygen or Fe(III) as an electron sink. The ability of this extremophile to accumulate poly(3-hydroxybutyrate) (PHB) and secrete extracellular polymeric substances (EPS) has also been reported. Hence, the aim of this work is to characterize the production of PHB and EPS by the wild strain DSM2389 using glycerol in shaken flasks and bioreactor. Results showed that maximum PHB accumulation (37-42% w/w) was obtained using glycerol concentrations of 9 and 15 g L-1, where maximum dry cell weight titers reached 3.6 and 3.9 g L-1, respectively. The culture in the bioreactor showed that PHB accumulation takes place under oxygen limitation, while the redox potential of the culture medium could be used for online monitoring of the PHB production. Recovered EPS was analyzed by Fourier-transform infrared spectroscopy and subjected to gas chromatography-mass spectrometry after cleavage and derivatization steps. These analyses showed the presence of sugars which were identified as mannose, rhamnose and glucose, in a proportion near to 3.2:2.3:1, respectively. Since glycerol had not been used in previous works, these findings suggest the potential of A. cryptum to produce biopolymers from this compound at a large scale with a low risk of microbial contamination due to the low pH of the fermentation process.


Rapid radioimmunoassay for methotrexate in biological fluids.
We report a radioimmunoassay for the cytostatic folic acid antagonist methotrexate. Antiserum was raised in rabbits immunized with a conjugate of methotrexate and methylated bovine serum albumin. The calibration curve of the assay is linear from 1 to 100 ng methotrexate per 100-mul sample, 0.1 ng methotrexate still inhibiting the binding of the tracer by 20%. The coefficient of variation ranged from 4.04% to 11.58%. The reaction of the antiserum proved to be specific for methotrexate, as only insignificant interference could be demonstrated with folic acid, folinic acid (leucovorin), or tetrahydrofolic acid. With the method, results are available about 20 h after blood sampling at a daily capacity of at least 48 samples (i.e., about 15 determinations), depending on the equipment. Concentrations of methotrexate in plasma and erythrocytes were determined in five patients who were on continuous treatment with the drug. In one patient the concentration/time curves were followed in plasma and erythrocytes by frequent determinations for 24 h after a parenteral dose. The results indicate that the procedure is well suited for clinical investigations.


Oxyphilic cell adenoma of parathyroid resulting in primary hyperparathyroidism and osteitis fibrosa cystica--a case report.
Adenomas of the parathyroid gland, the majority of which are of the solitary chief cell type, are the most frequent cause of primary hyperparathyroidism (pHPT). Parathyroid adenomas composed predominantly or exclusively of oxyphil cells are rare and most oxyphil cell adenomas of this organ remain clinically silent. We present here a case of hyperfunctioning oxyphil cell adenoma of the parathyroid gland resulting in pHPT, osteitis fibrosa cystica and simultaneous bilateral fractures upper shafts of femora.


The effects of intervention based on supportive leadership behaviour on Iranian nursing leadership performance: a randomized controlled trial.
To assess the effects of a workshop on supportive leadership behaviour (SLB) on the performance of head nurses, using a randomized controlled trial design. The effect of transformational leadership on SLB in nursing management is emphasised. A total of 110 head nurses working at university hospitals were included randomly in two control and intervention groups. The head nurses in the intervention group participated in supportive leadership training, but the control group did not. Performance in supportive leadership was assessed with a validated instrument, which six subordinates used to assess their head nurse (n = 731). There was a significant difference in SLB scores from baseline to the 3 month follow-up (P < 0.0001). Moreover, the post-intervention scores were significantly higher in the intervention group, compared with the control group (P < 0.0001). The results showed that in the intervention group, the effect sizes were greater for males (50%) than for females (36%) and greater for married participants (42%) than for single participants (37%). The workshop on supportive leadership behaviour, particularly the interactive multifaceted training, improved the leadership performance of the head nurses who participated in this study. Health policy decision makers should apply SLB, which is a significant leadership style, to improve the outcomes in other groups of health-care management, such as physicians. Future studies are needed to investigate the effects of such workshops in longer periods of follow up.


Proliferation of cultured human gingival fibroblasts caused by isradipine, a dihydropyridine-derivative calcium antagonist.
As it was reported earlier that isradipine, a Ca superset 2+ antagonist of dihydropyridine derivative class, caused regression of nifedipine-induced hyperplasia of human gingiva, experiments were performed to examine whether or not isradipine would solely inhibit the proliferation of cultured gingival fibroblasts. Normal human gingival fibroblast Gin-1 cells were used to test the impact of this medication. Fibroblast proliferation in the presence of isradipine (10 microM) was examined by using the reagent water-soluble tetrazolium-1 (WST-1). The level of basic fibroblast growth factor (bFGF) in the cell-free supernatant of each well was determined by using an enzyme-linked immunosorvent assay (ELISA) kit. The production of type I collagen was assayed by ELISA. Isradipine significantly enhanced the cell proliferation from the second day of the culture period. Also, isradipine raised the level of bFGF in the culture medium. The same concentration, also significantly enhanced the production of type I collagen. In conclusion, we were able to prove that isradipine causes the proliferation of cultured gingival fibroblasts as well as other dihydropyridine-derivative Ca superset 2+ antagonists do. In order to prevent the gingival overgrowth, it is advisable to be very careful in the use of isradipine as a therapy for hypertension and other indications.


Case report: Braid-like right coronary artery with chest pain.
Braid-like coronary artery is very rare. It is featured by the division of the coronary artery into multiple tortuous small channels that later converge into a normal lumen at any segment of the coronary artery. We presented a case of a 27-year-old male patient with occasional chest pain. In coronary CT angiography (CCTA) and coronary angiography, a braid-like appearance was found in the right coronary artery. After multidisciplinary discussion, it was speculated to be a woven coronary artery (WCA). We conducted a literature review about woven coronary arteries.


An Account of the Inaugural Tessier Skull Exhibition at the University of Paris Descartes.
Paul Tessier is widely regarded as the father of modern craniofacial surgery. Upon his passing in 2008, his private collection of human skulls was purchased by the French Association of Facial Surgeons to ensure the collection would remain in France. The first public exhibition of the skulls was held in the medical museum of the University of Paris Descartes in April 2014. From this collection of skulls and the imagination of Tessier an entirely new specialty was created. Modern craniofacial surgery, now is an integral part of any pediatric plastic surgery department. Cranial and facial osteotomies have also become commonplace in both traumatic and aesthetic surgery. The goals for craniofacial deformity are now a return to completely normal appearance and function, as Tessier always believed they should be.


Preoperative computed tomography-guided hookwire needle localization of a peritoneal multilocular inclusion cyst.
Preoperative hookwire localization of breast lesions is a well established technique to aid surgeons in localizing breast tumors. We describe the innovative use of a standard hookwire with CT guidance to localize an intraperitoneal inclusion cyst.


Overexpressed LAPTM4B-35 is a risk factor for cancer recurrence and poor prognosis in non-small-cell lung cancer.
The expression levels and clinical significances of Lysosomal-associated protein transmembrane-4β-35 (LAPTM4B-35) protein are unknown in the non-small-cell lung cancer (NSCLC). This study aimed to explore the expression and prognostic value of LAPTM4B-35 in NSCLC patients. The clinicopathological and survival data of 107 NSCLC patients who received radical surgery from 2007 and 2011 were reviewed. The LAPTM4B-35 expression of the paired tumors and adjacent normal specimens were detected, and the association between LAPTM4B-35 and clinical variables was explored. Kaplan-Meier analysis and Cox regression (Proportional hazard model) were performed to investigate the prognostic significance for NSCLC. LAPTM4B-35 was over expressed in NSCLC tissues. The elevated LAPTM4B-35 expression was associated with cancer recurrence (P = 0.031). The 5-year median OS and PFS were significantly worse in the LAPTM4B-35 overexpressed group. Multivariate Cox analysis showed that LAPTM4B-35 over-expression was an independent factor for OS and PFS in NSCLC(P = 0.018, P = 0.026, respectively). The overexpressed LAPTM4B-35 was an independent prognostic biomarker for NSCLC, which could predict cancer recurrence and poor over survival. And that may be applied as potential target for NSCLC treatment.


Imaging and differential diagnosis of masses within a joint.
Careful analysis of conventional radiographs remains the first step in the investigation of intra-articular abnormalities. However, other imaging techniques, such as ultrasonography, arthrography, computed tomography and magnetic resonance imaging, may add critical information that allows the correct diagnosis. The authors discuss the evaluation of masses within a joint on the basis of plain film analysis, as well as the contribution of additional imaging techniques to the differential diagnosis.


[18O]-labeled singlet oxygen as a tool for mechanistic studies of 8-oxo-7,8-dihydroguanine oxidative damage: detection of spiroiminodihydantoin, imidazolone and oxazolone derivatives.
A water-soluble [18O]-labeled endoperoxide derived from N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalene-dipropanamide (DHPN18O2) has been shown to act as a clean chemical source of [18O]-labeled molecular singlet oxygen. This allows the assessment of the singlet oxygen (1O2) reactivity toward biological targets such as DNA. The present work focuses on the qualitative identification of the main 1O2-oxidation products of 8-oxo-7,8-dihydro-2'-deoxyguanosine, which was achieved using high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Thus, the [18O]-labeled and unlabeled imidazolone and oxazolone, together with the diastereoisomeric spiroiminodihydantoin nucleosides, were detected as the main degradation products. In addition, a modified nucleoside that exhibits similar features as those of the oxidized guanidinohydantoin molecule was detected. Our data strongly suggest that the imidazolone and oxazolone nucleosides are generated via the rearrangement of an unstable 5-hydroperoxide intermediate. Interestingly, the combined use of appropriate tools, including isotopically labeled singlet oxygen and the high- resolution HPLC-ESI-MS/MS technique, has allowed to shed new light on the 1O2-mediated oxidation reactions of guanine DNA components.


GrainGenes 2.0. an improved resource for the small-grains community.
GrainGenes (http://wheat.pw.usda.gov) is an international database for genetic and genomic information about Triticeae species (wheat [Triticum aestivum], barley [Hordeum vulgare], rye [Secale cereale], and their wild relatives) and oat (Avena sativa) and its wild relatives. A major strength of the GrainGenes project is the interaction of the curators with database users in the research community, placing GrainGenes as both a data repository and information hub. The primary intensively curated data classes are genetic and physical maps, probes used for mapping, classical genes, quantitative trait loci, and contact information for Triticeae and oat scientists. Curation of these classes involves important contributions from the GrainGenes community, both as primary data sources and reviewers of published data. Other partially automated data classes include literature references, sequences, and links to other databases. Beyond the GrainGenes database per se, the Web site incorporates other more specific databases, informational topics, and downloadable files. For example, unique BLAST datasets of sequences applicable to Triticeae research include mapped wheat expressed sequence tags, expressed sequence tag-derived simple sequence repeats, and repetitive sequences. In 2004, the GrainGenes project migrated from the AceDB database and separate Web site to an integrated relational database and Internet resource, a major step forward in database delivery. The process of this migration and its impacts on database curation and maintenance are described, and a perspective on how a genomic database can expedite research and crop improvement is provided.


Estimation of reference intervals of insulin resistance (HOMA), insulin sensitivity (Matsuda), and insulin secretion sensitivity indices (ISSI-2) in Polish young people.
Insulin resistance is becoming an increasingly widespread problem worldwide. For its determination indirect indices of insulin resistance or insulin sensitivity have used. Those indices based on simultaneous measurements of blood glucose and insulin concentrations under fasting conditions or during the Oral Glucose Tolerance Test. The aim of the study was to estimate reliable reference values for the indices used in insulin resistance diagnosis. Materials and method. 191 selected participants, aged 18-31, were enrolled into the reference population. 130 participants from the reference population with fasting glucose ≤5.5 mmol/L, BMI<25 kg/m2, and without metabolic syndrome, were finally included in the reference group. The following insulin resistance indices were calculated: HOMA1-IR, HOMA2, HOMA2 from C-peptide, QUICKI, Matsuda Index and Insulin Secretion-Sensitive Index-2. Determination of reference intervals for indirect indices of insulin resistance was conducted in accordance with the C28-A3 procedure recommended by the Clinical & Laboratory Standards Institute (CLSI). Results. The reference intervals for indirect insulin resistance indices examined according to CLSI protocol were: ≤4.00, ≤2.27, ≤4.10, ≥0.31 for HOMA1-IR, HOMA2, HOMA2 C-pep., and QUICKI, respectively. For insulin sensitivity, the value of the Matsuda Index was established as ≥3.19 and for beta cell pancreatic function ISSI-2 as ≥206. Conclusions. Establishing a reference intervals for these indices enable the proper identification and differentiation of the types of insulin resistance in particular populations. The early detection of metabolic disorders allows for introduction of effective preventive action.


Can acute pain treatment reduce postsurgical comorbidity after breast cancer surgery? A literature review.
Regional analgesia, opioids, and several oral analgesics are commonly used for the treatment of acute pain after breast cancer surgery. While all of these treatments can suppress the acute postsurgical pain, there is growing evidence that suggests that the postsurgical comorbidity will differ in accordance with the type of analgesic used during the surgery. Our current study reviewed the effect of analgesics used for acute pain treatments on the major comorbidities that occur after breast cancer surgery. A considerable number of clinical studies have been performed to investigate the relationship between the acute analgesic regimen and common comorbidities, including inadequate quality of recovery after the surgery, persistent postsurgical pain, and cancer recurrence. Previous studies have shown that the choice of the analgesic modality does affect the postsurgical comorbidity. In general, the use of regional analgesics has a beneficial effect on the occurrence of comorbidity. In order to determine the best analgesic choice after breast cancer surgery, prospective studies that are based on a clear definition of the comorbidity state will need to be undertaken in the future.


Choline catabolism to glycine betaine contributes to Pseudomonas aeruginosa survival during murine lung infection.
Pseudomonas aeruginosa can acquire and metabolize a variety of molecules including choline, an abundant host-derived molecule. In P. aeruginosa, choline is oxidized to glycine betaine which can be used as an osmoprotectant, a sole source of carbon and nitrogen, and as an inducer of the virulence factor, hemolytic phospholipase C (PlcH) via the transcriptional regulator GbdR. The primary objective was to determine the contribution of choline conversion to glycine betaine to P. aeruginosa survival during mouse lung infection. A secondary objective was to gain insight into the relative contributions of the different roles of glycine betaine to P. aeruginosa survival during infection. Using a model of acute murine pneumonia, we determined that deletion of the choline oxidase system (encoded by betBA) decreased P. aeruginosa survival in the mouse lung. Deletion of the glycine betaine demethylase genes (gbcA-B), required for glycine betaine catabolism, did not impact P. aeruginosa survival in the lung. Thus, the defect of the betBA mutant was not due to a requirement for glycine betaine catabolism or dependence on a downstream metabolite. Deletion of betBA decreased the abundance of plcH transcript during infection, which suggested a role for PlcH in the betBA survival defect. To test the contribution of plcH to the betBA mutant phenotype a betBAplcHR double deletion mutant was generated. The betBA and betBAplcHR double mutant had a small but significant survival defect compared to the plcHR single mutant, suggesting that regulation of plcH expression is not the only role for glycine betaine during infection. The conclusion was that choline acquisition and its oxidation to glycine betaine contribute to P. aeruginosa survival in the mouse lung. While defective plcH induction can explain a portion of the betBA mutant phenotype, the exact mechanisms driving the betBA mutant survival defect remain unknown.


Keeping fat on time: Circadian control of adipose tissue.
Circadian clocks harmonize processes ranging from intracellular biochemistry to whole-body physiology in accordance with the Earth's 24h rotation. These intrinsic oscillators are based on an interlocked transcriptional-translational feedback loop comprised from a set of core clock factors. In addition to maintaining rhythmicity in nearly every cell of the body, these clock factors also mediate tissue specific metabolic functions. In this review, we will explore how the molecular clock shapes the unique features of different adipose depots.


GABA excitation in the adult brain: a mechanism for excitation- neurogenesis coupling.
The production of new neurons in the adult hippocampus is exquisitely regulated, and alterations in this process may underlie both normal and pathological hippocampal function. In this issue of Neuron, Tozuka et al. describe electrophysiological recordings that target proliferating progenitor cells in adult mouse hippocampal slices. They report that GABAergic synaptic inputs directly depolarize the proliferating progenitors, thereby activating molecular players that favor neuronal differentiation and providing a mechanism for direct excitation-neurogenesis coupling in vivo.


Variation in the calpain-10 gene is associated with elevated triglyceride levels and reduced adipose tissue messenger ribonucleic acid expression in obese Swedish subjects.
Our aim was to investigate the possible role of the type 2 diabetes susceptibility gene CAPN10 in obesity. A case control study consisting of 235 obese Swedish subjects [body mass index, 40 (35-45) kg/m(2)] and 235 controls matched for age and gender [body mass index, 22 (21-24) kg/m(2)], and a transmission disequilibrium test consisting of 116 parents-offspring trios, where the offspring was abdominally obese [waist, 100 (95-110) cm], were performed. CAPN10 mRNA expression was studied in adipose tissue biopsies from 33 of the obese subjects participating in the case control study. The CAPN10 single-nucleotide polymorphism (SNP)-43 was genotyped using PCR followed by NdeI digestion or by allelic discrimination. CAPN10 mRNA levels were quantified using real-time RT-PCR with Cyclophilin A as an internal standard. No significant associations between CAPN10 SNP-43 and obesity were seen, neither in the case control study nor in the transmission disequilibrium test, but obese subjects homozygous for the SNP-43 G allele had significantly elevated triglyceride levels compared with subjects carrying the A allele [1.7 (1.1-2.4) vs. 1.4 (1.0-2.0); P = 0.03]. The CAPN10 mRNA expression in sc fat was significantly reduced in subjects with the SNP-43 G/G genotype compared with carriers of SNP-43 G/A (G/G, 0.33 +/- 0.02, vs. G/A, 0.51 +/- 0.09; P = 0.048), and a similar trend was observed in visceral fat (G/G, 0.52 +/- 0.06, vs. G/A, 0.65 +/- 0.10; P = 0.22). Our data suggest that reduced CAPN10 expression may be a risk factor for features associated with the metabolic syndrome in obese subjects, although variation in the gene does not seem to contribute to the risk for developing obesity per se.


FDI based on Artificial Neural Network for Low-Voltage-Ride-Through in DFIG-based Wind Turbine.
As per modern electrical grid rules, Wind Turbine needs to operate continually even in presence severe grid faults as Low Voltage Ride Through (LVRT). Hence, a new LVRT Fault Detection and Identification (FDI) procedure has been developed to take the appropriate decision in order to develop the convenient control strategy. To obtain much better decision and enhanced FDI during grid fault, the proposed procedure is based on voltage indicators analysis using a new Artificial Neural Network architecture (ANN). In fact, two features are extracted (the amplitude and the angle phase). It is divided into two steps. The first is fault indicators generation and the second is indicators analysis for fault diagnosis. The first step is composed of six ANNs which are dedicated to describe the three phases of the grid (three amplitudes and three angle phases). Regarding to the second step, it is composed of a single ANN which analysis the indicators and generates a decision signal that describes the function mode (healthy or faulty). On other hand, the decision signal identifies the fault type. It allows distinguishing between the four faulty types. The diagnosis procedure is tested in simulation and experimental prototype. The obtained results confirm and approve its efficiency, rapidity, robustness and immunity to the noise and unknown inputs.


Corneal nerve fiber size adds utility to the diagnosis and assessment of therapeutic response in patients with small fiber neuropathy.
Small fiber neuropathy (SFN) is a common feature of many inflammatory diseases, often presenting with pain and disability. SFN is diagnosed using symptoms, thermal threshold testing, and intra-epidermal nerve fiber quantification. Corneal confocal microscopy (CCM) is an ophthalmic imaging technique which non-invasively quantifies corneal nerve fiber (CNF) density, branch density and length, and has comparable diagnostic and superior ability to identify nerve regeneration compared to skin biopsy. CNF size (width and area) depends upon the number of fibers within each nerve, as well as pathology (e.g., swelling), and may provide additional sensitivity to diagnose SFN and identify nerve repair. We have compared the utility of the standard CCM variables employed to CNF size in patients with diabetic sensorimotor polyneuropathy or sarcoidosis-associated SFN, and in patients with SFN following cibinetide administration, an agent which promotes nerve repair. The results show that: 1) CNF width distribution and area depend upon neuropathy severity; 2) CNF area, density, branch density and length possess comparable discriminatory power for diagnosing neuropathy; 3) CNF area is related to length by a quadratic function which is predictive for both healthy subjects and those with SFN; 4) CNF area is a useful variable for quantifying change in CNF morphology.


Proteomic signatures for perioperative oxygen delivery in skin after major elective surgery: mechanistic sub-study of a randomised controlled trial.
Maintaining adequate oxygen delivery (DO2) after major surgery is associated with minimising organ dysfunction. Skin is particularly vulnerable to reduced DO2. We tested the hypothesis that reduced perioperative DO2 fuels inflammation in metabolically compromised skin after major surgery. Participants undergoing elective oesophagectomy were randomised immediately after surgery to standard of care or haemodynamic therapy to achieve their individualised preoperative DO2. Abdominal punch skin biopsies were snap-frozen before and 48 h after surgery. On-line two-dimensional liquid chromatography and ultra-high-definition label-free mass spectrometry was used to characterise the skin proteome. The primary outcome was proteomic changes compared between normal (≥preoperative value before induction of anaesthesia) and low DO2 (<preoperative value before induction of anaesthesia) after surgery. Secondary outcomes were functional enrichment analysis of up/down-regulated proteins (Ingenuity pathway analysis; STRING Protein-Protein Interaction Networks). Immunohistochemistry and immunoblotting confirmed selected proteomic findings in skin biopsies obtained from patients after hepatic resection. Paired punch skin biopsies were obtained from 35 participants (mean age: 68 yr; 31% female), of whom 17 underwent oesophagectomy. There were 14/2096 proteins associated with normal (n=10) vs low (n=7) DO2 after oesophagectomy. Failure to maintain preoperative DO2 was associated with upregulation of proteins counteracting oxidative stress. Normal DO2 after surgery was associated with pathways involving leucocyte recruitment and upregulation of an antimicrobial peptidoglycan recognition protein. Immunohistochemistry (n=6 patients) and immunoblots after liver resection (n=12 patients) supported the proteomic findings. Proteomic profiles in serial skin biopsies identified organ-protective mechanisms associated with normal DO2 after major surgery. ISRCTN76894700.


Dealing with an Unconventional Genetic Code in Mitochondria: The Biogenesis and Pathogenic Defects of the 5-Formylcytosine Modification in Mitochondrial tRNAMet.
Human mitochondria contain their own genome, which uses an unconventional genetic code. In addition to the standard AUG methionine codon, the single mitochondrial tRNA Methionine (mt-tRNAMet) also recognises AUA during translation initiation and elongation. Post-transcriptional modifications of tRNAs are important for structure, stability, correct folding and aminoacylation as well as decoding. The unique 5-formylcytosine (f5C) modification of position 34 in mt-tRNAMet has been long postulated to be crucial for decoding of unconventional methionine codons and efficient mitochondrial translation. However, the enzymes responsible for the formation of mitochondrial f5C have been identified only recently. The first step of the f5C pathway consists of methylation of cytosine by NSUN3. This is followed by further oxidation by ABH1. Here, we review the role of f5C, the latest breakthroughs in our understanding of the biogenesis of this unique mitochondrial tRNA modification and its involvement in human disease.


Implementation of a hospice pain-education programme.
No studies have explored the pain resource nurse curriculum in the hospice setting. This curriculum offers a structured method to teach pain management to nurses. The purpose of this study was to examine the effect of implementing a modified pain resource nurse curriculum on nursing knowledge in a community hospice agency. A modified and condensed version of the pain resources nurse curriculum was presented to community hospice nurses during two educational sessions. A pre-test-post-test assessment was conducted using a modified version of the Nursing Knowledge and Attitudes Survey Regarding Pain tool to assess knowledge growth from the educational sessions. For educational session 1, average correct responses rose slightly from the pre-test to the post-test. However, this increase was not found to be statistically significant. For educational session 2, average correct responses rose an average of 2.6 points. This increase was found to be statistically significant. Based on this pre-experimental study, there is evidence that the pain resources nurse curriculum can provide an instructional framework for teaching hospice nurses. However, further study is needed, including a more rigorous design.


Fatty acid composition of serum lipids in patients with a coronary bypass operation.
The fatty acid composition of serum phospholipids and cholesteryl esters was analysed in 71 male patients with angiographically defined three-vessel coronary artery disease (CAD) selected for a coronary bypass operation. Their 71 control subjects were matched according to age, sex, smoking, relative weight, and absence of CAD. The concentrations of fatty acids, 14:0, 16:0 and 16:1 of the serum phospholipids, were significantly (P less than 0.01, P less than 0.05 and P less than 0.01, respectively) higher in CAD patients than in the controls. On the other hand, linoleic (18:2 omega 6), linolenic (18:3 omega 3) and arachidonic (20:4 omega 6) acids were at a significantly lower level in the patients when compared to the controls. The polyunsaturated/saturated fatty acids (P/S) ratio in serum phospholipids was significantly (P less than 0.01) lower in the patients than in the controls. In the cholesteryl ester fraction the results paralleled those of the phospholipids. Significant correlations were obtained between the polyunsaturated fatty acids and the high density lipoprotein cholesterol or apolipoprotein A-I in the control subjects but most of these correlations were absent in the patients. Our present results further support the importance of linoleic acid in the protection against atherosclerosis. However, no unequivocal evidence on the possible beneficial effect of long-chain omega 3-fatty acids in comparison with omega 6-acids was obtained.


ErbB-3 and ErbB-4 function as the respective low and high affinity receptors of all Neu differentiation factor/heregulin isoforms.
Neu differentiation factor (NDF or heregulin) elevates tyrosine phosphorylation of the ErbB-2 receptor tyrosine kinase, and it was, therefore, thought to function as a ligand of this receptor. However, several lines of evidence raised the possibility that the interaction between NDF and ErbB-2 involves another molecule, which belongs to the family of epidermal growth factor receptors. To address this question we constructed soluble chimeric proteins between alkaline phosphatase and the extracellular domains of ErbB-2 and either ErbB-3 or ErbB-4, two newly recognized members of the epidermal growth factor receptor family. Using the soluble proteins we found that beta isoforms of NDF specifically bind to the ErbB-3 and ErbB-4 receptors but not to the soluble ErbB-2 protein. When ectopically expressed in monkey fibroblasts, the full-length ErbB-3 and ErbB-4 receptors conferred specific binding to NDF. In these cells ErbB-3 displayed lower ligand binding affinity than ErbB-4, but like the latter receptor it preferred to bind the beta isoform over the alpha class of NDFs. These results indicate that both ErbB-3 and ErbB-4 function as physiological receptors of all NDF isoforms and suggest that a still unknown ligand of ErbB-2 exists.


How generic is iodide-tagging photoelectron spectroscopy: An extended investigation on the Gly·X- (Gly = glycine, X = Cl or Br) complexes.
We report a joint negative ion photoelectron spectroscopy (NIPES) and quantum chemical computational study on glycine-chloride/bromide complexes (denoted Gly·X-, X = Cl/Br) in close comparison to the previously studied Gly·I- cluster ion. Combining experimental NIPE spectra and theoretical calculations, various Gly·X- complexes were found to adopt the same types of low-lying isomers, albeit with different relative energies. Despite more congested spectral profiles for Gly·Cl- and Gly·Br-, spectral assignments were accomplished with the guidance of the knowledge learned from Gly·I-, where a larger spin-orbit splitting of iodine afforded well-resolved, recognizable spectral peaks. Three canonical plus one zwitterionic isomer for Gly·Cl- and four canonical conformers for Gly·Br- were experimentally identified and characterized in contrast to the five canonical ones observed for Gly·I- under similar experimental conditions. Taken together, this study investigates both genericity and variations in binding patterns for the complexes composed of glycine and various halides, demonstrating that iodide-tagging is an effective spectroscopic means to unravel diverse ion-molecule binding motifs for cluster anions with congested spectral bands by substituting the respective ion with iodide.


Pathophysiology of pulsatile and copulsatile release of thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and alpha-subunit.
Under physiological conditions, TSH, LH, FSH, and alpha-subunit are released in discrete pulses. To further characterize their neuroregulation and to investigate possible copulsatile secretion of these glycoprotein hormones, we studied the 24-h pulse profiles of all four hormones in each of four subject groups: young men, young women, postmenopausal women, and subjects with untreated primary hypothyroidism. Gonadotropin pulse properties in euthyroid men and women were similar to those previously reported, and hypothyroid subjects had normal gonadotropin pulse patterns. TSH release was pulsatile in all groups; hypothyroid subjects had increased pulse amplitude, but loss of the usual nocturnal increases in pulse amplitude. alpha-Subunit concentrations were pulsatile in all groups, with minimal circadian variation; postmenopausal and hypothyroid subjects had increased alpha-subunit pulse amplitude. We then tested pulse concordance among the four simultaneous hormone series. alpha-Subunit and the gonadotropins were significantly coreleased (triple coincidence), suggesting that all three hormones are closely linked to processes that regulate GnRH secretion. alpha-Subunit bursts were also significantly coincident with those of TSH in men, postmenopausal women, and hypothyroid subjects. Interestingly, TSH pulses were significantly concordant with those of LH and FSH, and all four hormones were significantly concordant in men, postmenopausal women, and hypothyroid subjects. In conclusion, the present findings imply that an underlying unified signal coordinates pulsatile hormone secretion from both gonadotrophs and thyrotrophs.


Cell interactions in microgravity: cytotoxic effects of natural killer cells in vitro.
To study cell-to-cell interactions in microgravity we examined the functional activity of natural killer cells on board of the ISS. NK cells are the effector cells with direct cytotoxic activity to oncogenic, virus-infected cells and cells with modified differentiation. Ground-based experiments have shown that the examination of target cell lysis after incubation with NK cells is a simple and informative model for studying the influence of microgravity. NK cytotoxicity was measured as the value of non-degradeted labeled myeloblasts (K-562) after 24 hrs exposure with human lymphocytes in suspension. A special device was developed for space flight experiments. Human cultured lymphocytes and labeled K-562 cells were loaded into special syringes and delivered to the Russian segment of the ISS. Cosmonauts prepared co-cultured suspensions during the first day of microgravity, exposed them at 37 degrees C for 24 hrs and then separated H3-labeled cells on special filters. The results of ISS-8 mission showed that human NK cells in vitro remain lysis activity toward target cells in microgravity. The basal level of NK cytotoxicity was low and we did not found significant differences between "control" and "flight" values. Interferon production during the interaction between immune and target cells (ratio 10:1) in microgravity did not differ compared with ground-based control experiments. Ground exposure of the same lymphocyte samples with K-562 cells to 24 hrs clinorotation also did not lead to significant differences. These experiments paved the way for understanding the cell interaction mechanisms in space flight and the obtained results suggest that microgravity does not disrupt the interaction of NK cells with tumor cells.


Nerve growth factor induces increased airway inflammation via a neuropeptide-dependent mechanism in a transgenic animal model of allergic airway inflammation.
Nerve growth factor (NGF) exerts an important functional impact on the pathogenesis of allergic diseases. Data obtained in animal models of allergic bronchial asthma indicate that NGF alters sensory nerve function and promotes allergic inflammation, bronchial hyper-reactivity, and airway obstruction. To further delineate the effects of NGF on airway inflammation, we employed a transgenic (tg) animal model of allergic inflammation and asthma. NGF-tg mice, which overexpress NGF in Clara cells of the airways, were compared with wild-type (wt) littermates regarding their ability to mount IgE-related airway inflammatory responses. Mice were sensitized intraperitoneally to ovalbumin (OVA) and locally challenged via the airways according to established protocols. NGF-tg mice displayed enhanced levels of OVA-specific IgE antibody titres after repeated OVA aerosol exposure. In the airways, increased numbers of eosinophils were detected. These results were confirmed to be NGF specific, because similar results were obtained following local application of NGF into the airways of wt mice. The effect of NGF was partly mediated via neuropeptides, as treatment of OVA-sensitized NGF-tg mice with the dual neurokinin (NK) receptor NK-1/NK-2 antagonist partly prevented enhanced airway inflammation. The present data indicate an important functional role of NGF in allergic airway inflammation and point to an involvement of tachykinins as mediators of NGF effects.


Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab.
Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC.


Further user comments regarding usage of an interactive educational diabetes simulator (AIDA).
This "Diabetes Information Technology & WebWatch" column continues the diabetes simulation theme from previous issues and overviews various user experience with the AIDA v4 interactive educational freeware diabetes simulator. AIDA is a diabetes computer program that permits the interactive simulation of plasma insulin and blood glucose (BG) profiles for educational, demonstration, and self-learning purposes. It has been made freely available, without charge, via the Web as a noncommercial contribution to continuing diabetes education. Since its Internet launch in 1996, over 145,000 visits have been logged at the AIDA Website--www.2aida.org--and over 29,000 copies of the program have been downloaded, free of charge. While these statistics may appear impressive, they do not tell the personal story of how people have been making use of the software, and what they actually think about the program. In this respect, this column documents some of the independent user comments about AIDA sent in spontaneously via electronic mail (email) by patients with diabetes and their relatives, as well as by health-care professionals. Comments posted to diabetes newsgroups and diabetes email lists, as well as a selection of those which have been found at other, linked, diabetes Websites are also highlighted.


Odor Fingerprint Analysis Using Feature Mining Method Based on Olfactory Sensory Evaluation.
In this paper, we aim to use odor fingerprint analysis to identify and detect various odors. We obtained the olfactory sensory evaluation of eight different brands of Chinese liquor by a lab-developed intelligent nose. From the respective combination of the time domain and frequency domain, we extract features to reflect the samples comprehensively. However, the extracted feature combined time domain and frequency domain will bring redundant information that affects performance. Therefore, we proposed data by Principal Component Analysis (PCA) and Variable Importance Projection (VIP) to delete redundant information to construct a more precise odor fingerprint. Then, Random Forest (RF) and Probabilistic Neural Network (PNN) were built based on the above. Results showed that the VIP-based models achieved better classification performance than PCA-based models. In addition, the peak performance (92.5%) of the VIP-RF model had a higher classification rate than the VIP-PNN model (90%). In conclusion, odor fingerprint analysis using a feature mining method based on the olfactory sensory evaluation can be applied to monitor product quality in the actual process of industrialization.


Using patient-centered endpoints to determine the cost-effectiveness of triptans for acute migraine therapy.
The objective of this study was to use the patient-centered efficacy measurements of sustained pain free and sustained pain free with no adverse events to compare the relative cost-effectiveness of 6 oral triptans in the treatment of acute migraine. Adverse event and sustained pain-free rates were obtained from a comprehensive meta-analysis of 53 clinical trials of oral triptans. Efficacy and tolerability were assumed to be independent. Average wholesale prices were in US dollars as of May 10, 2004. The meta-analysis of oral triptans reported that almotriptan 12.5 mg (Axert) exhibited the highest sustained pain-free rate (25.9%), with the lowest rate associated with eletriptan 20 mg (Relpax) (10.6%). In addition, almotriptan 12.5 mg possessed the lowest overall absolute adverse event rate (14.2%), with the highest adverse event rate exhibited by eletriptan 80 mg (53.9%). To attain 100 sustained pain-free patients, almotriptan 12.5 mg and rizatriptan 10 mg (Maxalt) proved to be the most cost-effective triptans, costing $7120 and $7427, respectively; the least cost-effective were naratriptan 2.5 mg (Amerge) ($13,736) and eletriptan 20 mg ($16,104). To attain 100 sustained pain-free with no adverse events patients, almotriptan 12.5 mg was the most cost-effective triptan ($8298) and the least cost-effective were eletriptan 20 mg ($25,521) and eletriptan 80 mg ($29,614). At average wholesale prices as of May 10, 2004, almotriptan 12.5 mg achieved the highest level of cost-effectiveness using either sustained pain free or sustained pain free with no adverse events as endpoints.


A general method for the generation of high-titer, pantropic retroviral vectors: highly efficient infection of primary hepatocytes.
Retroviral vectors have been central components in many studies leading to human gene therapy. However, the generally low titers and inefficient infectivity of retroviral vectors in human cells have limited their use. We previously reported that the G protein of vesicular stomatitis virus can serve as the exclusive envelope protein component for one specific retroviral vector, LGRNL, that expresses vesicular stomatitis virus G. We now report a more useful general transient transfection scheme for producing very high-titer vesicular stomatitis virus G-enveloped pseudotypes from any Moloney murine leukemia-based retroviral vector without having to rely on the expression of the cytotoxic G protein from the retroviral vector itself. We also demonstrate very high efficiency of infection with a pseudotyped lacZ vector in primary mouse hepatocytes. We suggest that pseudotyped retroviral vectors carrying reporter genes will permit genetic studies in many previously inaccessible vertebrate and invertebrate systems. Furthermore, because these vectors represent retroviral vectors of sufficiently high titer to allow efficient direct retroviral-mediated in vivo gene transfer, we also suggest that pseudotyped vectors carrying potentially therapeutic genes will become useful to test the potential for in vivo gene therapy.


Status of market, regulation and research of genetically modified crops in Chile.
Agricultural biotechnology and genetically modified (GM) crops are effective tools to substantially increase productivity, quality, and environmental sustainability in agricultural farming. Furthermore, they may contribute to improving the nutritional content of crops, addressing needs related to public health. Chile has become one of the most important global players for GM seed production for counter-season markets and research purposes. It has a comprehensive regulatory framework to carry out this activity, while at the same time there are numerous regulations from different agencies addressing several aspects related to GM crops. Despite imports of GM food/feed or ingredients for the food industry being allowed without restrictions, Chilean farmers are not using GM seeds for farming purposes because of a lack of clear guidelines. Chile is in a rather contradictory situation about GM crops. The country has invested considerable resources to fund research and development on GM crops, but the lack of clarity in the current regulatory situation precludes the use of such research to develop new products for Chilean farmers. Meanwhile, a larger scientific capacity regarding GM crop research continues to build up in the country. The present study maps and analyses the current regulatory environment for research and production of GM crops in Chile, providing an updated overview of the current status of GM seeds production, research and regulatory issues.


Heme synthesis in yeast does not require oxygen as an obligatory electron acceptor.
In a previous paper (Krawiec, Z., Biliński, T., Schüller, C. & Ruis, H., 2000, Acta Biochim. Polon. 47, 201-207) we have shown that catalase T holoenzyme is synthesized in the absence of oxygen after treatment of anaerobic yeast cultures with 0.3 M. NaCl, or during heat shock. This finding suggests that heme moiety of the enzyme can either be formed de novo in the absence of oxygen, or derives from the preexisting heme pool present in cells used as inoculum. The strain bearing hem1 mutation, resulting in inability to form delta-aminolevulinate (ALA), the first committed precursor of heme, was used in order to form heme-depleted cells used as inocula. The cultures were supplemented with ALA at the end of anaerobic growth prior the stress treatment. The appearance of active catalase T in the stressed cells strongly suggests that heme moiety of catalase T is formed in the absence of oxygen. This finding suggests the necessity to reconsider current opinions concerning mechanisms of heme synthesis and the role of heme as an oxygen sensor.


Comparison of keratometric and pachymetric parameters with Scheimpflug imaging in normal and keratoconic Asian eyes.
To evaluate the keratometric and pachymetric parameters of keratoconic corneas of Asian eyes with the Scheimpflug imaging camera. This is a cross-sectional study of 22 eyes with Amsler-Krumeich stage 1 keratoconus and 48 eyes from normal subjects conducted in a tertiary eye hospital. A rotating Scheimpflug imaging system, the Pentacam, was used to evaluate all eyes for tomographic parameters, as well as pachymetric progression indices (PPI) and Ambrósio relational thickness (ART). All PPI and ART parameter values were significantly different between study and control groups. Cornea minimum radius of curvature, absolute distance from corneal apex to thinnest location, as well as the distance from corneal apex to thinnest location in Y-axis also demonstrated statistically significant differences. The mean ART values for keratoconus eyes were 241 μm (ART-maximum) and 352 μm (ART-average), falling within previously reported best cutoff values for detecting keratoconus. On receiver operating characteristics curve analysis, the area under the curve values were highest for PPI and ART parameters. There are significant differences in tomographic parameters between stage 1 keratoconic and normal Asian eyes. Pachymetric indices such as the PPI and the ART index can serve as additional tools in differentiating keratoconic from normal eyes. The findings validate the usefulness of the ART in identifying keratoconic eyes in Asians.


Prognostic factors and clinical features in liveborn neonates with hydrops fetalis.
The purpose of this study was to delineate the etiology and the clinical features of liveborn neonates with hydrops fetalis, and to explore the prognostic factors for survival. Medical records of 28 liveborn neonates with hydrops fetalis between April 1995 and March 2005 were reviewed retrospectively. Demographic data, clinical manifestations, laboratory findings, and outcomes were analyzed. Most patients presented with pleural effusions (21 of 28) and ascites (22 of 28). The majority of patients had hydrops due to cardiovascular diseases (seven of 28), hematologic disorders (six of 28), lymphatic malformations (six of 28), and idiopathic origins (six of 28). The overall survival rate was 50% and was highest (83%) in infants with lymphatic malformations. By univariate analysis, risk factors for mortality are earlier ages at diagnosis and at birth, low Apgar scores, need for resuscitation in the delivery room, low serum albumin level, and severe acidemia. After using stepwise multiple logistic regression analysis, the most significant factors associated with fatality were younger gestational age at birth and lower serum albumin level. Hydrops fetalis remains a complex condition with a high mortality rate. Hydrops resulting from lymphatic malformations has a favorable outcome. Preterm birth at less than 34 weeks and serum albumin concentration lower than 2 g/dL are two poor prognostic factors for survival.


Modulation of DNA vaccine-elicited CD8+ T-lymphocyte epitope immunodominance hierarchies.
Generating broad cellular immune responses against a diversity of viral epitopes is a major goal of current vaccine strategies for human immunodeficiency virus type 1 (HIV-1) and other pathogens. Virus-specific CD8(+) T-lymphocyte responses, however, are often highly focused on a very limited number of immunodominant epitopes. For an HIV-1 vaccine, the breadth of CD8(+) T-lymphocyte responses may prove to be critical as a result of the need to cover a wide diversity of viral isolates in the population and to limit viral escape from dominant epitope-specific T lymphocytes. Here we show that epitope modification strategies can alter CD8(+) T-lymphocyte epitope immunodominance hierarchies elicited by a DNA vaccine in mice. Mice immunized with a DNA vaccine expressing simian immunodeficiency virus Gag lacking the dominant D(b)-restricted AL11 epitope generated a marked and durable augmentation of responses specific for the subdominant D(b)-restricted KV9 epitope. Moreover, anatomic separation strategies and heterologous prime-boost regimens generated codominant responses against both epitopes. These data demonstrate that dominant epitopes can dramatically suppress the immunogenicity of subdominant epitopes in the context of gene-based vaccines and that epitope modification strategies can be utilized to enhance responses to subdominant epitopes.


Incidence of cardiovascular events and associated risk factors in kidney transplant patients: a competing risks survival analysis.
The high prevalence of cardiovascular risk factors among the renal transplant population accounts for increased mortality. The aim of this study is to determine the incidence of cardiovascular events and factors associated with cardiovascular events in these patients. An observational ambispective follow-up study of renal transplant recipients (n = 2029) in the health district of A Coruña (Spain) during the period 1981-2011 was completed. Competing risk survival analysis methods were applied to estimate the cumulative incidence of developing cardiovascular events over time and to identify which characteristics were associated with the risk of these events. Post-transplant cardiovascular events are defined as the presence of myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances, peripheral vascular disease and cardiovascular disease and death. The cause of death was identified through the medical history and death certificate using ICD9 (390-459, except: 427.5, 435, 446, 459.0). The mean age of patients at the time of transplantation was 47.0 ± 14.2 years; 62% were male. 16.5% had suffered some cardiovascular disease prior to transplantation and 9.7% had suffered a cardiovascular event. The mean follow-up period for the patients with cardiovascular event was 3.5 ± 4.3 years. Applying competing risk methodology, it was observed that the accumulated incidence of the event was 5.0% one year after transplantation, 8.1% after five years, and 11.9% after ten years. After applying multivariate models, the variables with an independent effect for predicting cardiovascular events are: male sex, age of recipient, previous cardiovascular disorders, pre-transplant smoking and post-transplant diabetes. This study makes it possible to determine in kidney transplant patients, taking into account competitive events, the incidence of post-transplant cardiovascular events and the risk factors of these events. Modifiable risk factors are identified, owing to which, changes in said factors would have a bearing of the incidence of events.


Utilization of dental health services by Danish adolescents attending private or public dental health care systems.
The objectives of the study were: 1) to describe the choice of dental care system among 16-year-olds, 2) to describe the utilization of dental services among 16-17-year-olds enrolled in either public or private dental care systems, and to compare the dental services provided by the alternative systems. The study comprised 1,245 adolescents from 3 municipalities; the historical cohort study design was applied; and data were collected from dental records (public dental service) and dental claims (private practice). At age 16, 12% preferred being enrolled in the private practice system, while 88% remained in the public dental care system. During the 2-year study period the attendance rate was 99% for the public system, while 90% attended the private practice system (P< 0.001). Preventive dental services were provided more frequently by the public than the private system (P< 0.001). Despite the fact that the economic barrier was eliminated a lower attendance rate was observed for patients transferred to the private practice system.


Contribution of rating scales to the assessment of executive functions.
Executive functions play a vital role in the everyday functioning of healthy individuals across the lifespan and have been implicated in a wide variety of clinical conditions. Historically, the assessment of executive functions in clinical and research settings relied on performance-based measures. A number of authors have argued, however, that such measures have limited ecological validity. In response to this limitation of performance-based measures, several rating scales have been developed that seek to gauge a person's or their knowledgeable informant's (e.g., parent or teacher) subjective view of executive functioning in everyday life. In this article we review evidence supporting the use of rating scales of executive function including profiles in clinical populations, biological correlates, relationships to relevant outcome measures such as academic performance, and correlations with performance-based measures. We conclude that performance-based and rating scale measures provide complementary information with respect to a child's executive functions, offering a more comprehension view than either approach alone.


Calcium Channel Blockers- Induced Iatrogenic Gingival Hyperplasia: Case Series.
Hypertension rightfully termed as "Silent killer" is associated with increase in morbidity and mortality when left untreated. Calcium channel blockers are the most commonly prescribed first-line anti-hypertensive drugs in India. Calcium channel blockers are known to cause gingival hyperplasia but with lower incidence rates compared to the other two groups causing iatrogenic gingival overgrowth, immunosuppressants, and anticonvulsants. Nifedipine administration, among the calcium channel blockers, has been frequently associated with iatrogenic gingival hyperplasia. Incidence of amlodipine-induced gingival hyperplasia which has similar pharmacodynamic action like nifedipine, had been reported rarely. Here, we present a case series of drug induced gingival overgrowth caused by calcium channel blockers used for the management of hypertension. All the patient's condition improved after withdrawal of the offending drug, oral prophylaxis and intervention, and alternate drug from other first-line drugs were started for managing hypertension.


Economic evaluation of a Ninngen-dokku (medical checkup).
An economic evaluation of a medical checkup center (Ninngen-dokku, "human dry dock") was conducted from two perspectives: the cost for cancer checkup, and the cost for medical treatment after a diagnosis was obtained. We studied the cost of diagnosing cancer, compared with the cost required when cancer of an individual organ was detected through mass health testing, and studied the economics of a Ninngen-dokku according to Kawai's method of medical judgment. Assuming that the cost of death is more than the cost of saving the lives of persons who undergo the Ninngen-dokku, the Ninngen-dokku will be affordable. In the group undergoing the Ninngen-dokku compared with the group which did not, the estimated cost of medical treatment was reduced. The Ninngen-dokku carries advantages that cannot be quantified in financial terms; therefore, a multi-layered economic analysis of the Ninngen-dokku was required.